Gerhard Glatting

2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma

The authors undertook a prospective evaluation of the clinical value of 2‐fluoro [18‐]‐2‐deoxyglucose positron emission tomography (FDG‐PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB).

FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters

Abstract. The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c-erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6–122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4–22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%±13.8% (median 10%, range 0%–60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer (P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c-erb B2 (P=0.79), p53 (P=0.92), tumour grading (P=0.09), oestrogen receptor status (P=0.41), progesterone receptor status (P=0.34), axillary lymph node status (P=0.90) and tumour size (P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer (P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining (P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.

F-18 NaF PET for Detection of Bone Metastases in Lung Cancer: Accuracy, Cost-Effectiveness, and Impact on Patient Management†

As bone metastases might be present in lung cancer despite a normal bone scan, we examined various alternatives prospectively. Positron emission tomography using F‐18 sodium fluoride (PET) and single photon emission tomography (SPECT) were more sensitive than a planar bone scan. PET was more accurate with a shorter examination time than SPECT but had higher incremental costs.

Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer.

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19–39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14–22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

PurposeIn detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18F-fluorodihydroxyphenylalanine (18F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone.Methods18F-DOPA PET, CT and 18F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology.ResultsOf the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value.Conclusion18F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18F-DOPA PET or CT alone.

Blurring of vessels in spiral CT angiography : Effects of collimation width, pitch, viewing plane, and windowing in maximum intensity projection

PURPOSE Our goal was to examine the effects of collimation width (CW), pitch, viewing plane, and windowing on the display of in-plane vessels in maximum intensity projection (MIP). METHOD A theoretical concept based on partial volume averaging of vessels was developed to describe the contents of voxels (densities) in MIP and to derive cross-sectional vessel diameters and blurring. To validate the concept and to describe the influence of pitch, a Plexiglas cone submerged in water was scanned with varying CW and pitch. Binary MIP with three representative window levels was chosen so that definitive vessel diameters could be quantitated. RESULTS The theoretical concept correctly predicted voxel contents and blurring for CW > or = 3 mm and low pitch. For high pitch, actual blurring was larger; however, for a given table speed, blurring of the cone decreased with pitch while increasing with CW. Overall blurring was most effectively reduced by using a thin CW and the transverse viewing plane. In the transverse viewing plane, the least blurring was found using binary MIP with a low window level. On the contrary, in the longitudinal viewing plane, blurring was minimized using a window level halfway between the density of the cone and that of the surrounding water. CONCLUSION For CW > or = 3 mm, blurring of in-plane vessels can be explained with a simple geometrical concept based on partial volume. For accurate display, the transverse viewing plane should be used, a proper windowing must be chosen, and the CW should be kept below vessel size while raising the pitch to cover a reasonable volume.

Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [11C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left‐sided symptoms was studied using fluorodeoxyglucose (FDG) and [11C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [11C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.

F-18 Fluorodeoxyglucose (FDG) and C-Reactive Protein (CRP)

This study was done to evaluate if the accuracy of FDG-PET concerning the differentiation of benign and malignant pancreatic masses differs for patients with and without elevated C-Reactive Protein (CRP). Three hundred-four patients (165 neoplasms, 98 chronic pancreatitis, and 41 benign lesions) received FDG-PET of the abdomen prior to planned resective surgery. CRP was unknown, normal, and elevated with 211, 71, and 22 patients, respectively. For differentiation of benign and malignant lesions, specificity was 87% for patients with unknown or normal CRP, and it was 40% for patients with elevated CRP (P < 0.01). Thirty-five percent of those patients with both a positive PET and elevated CRP were false positive. On the contrary, sensitivity was slightly higher in the group with elevated CRP (92% vs. 80%, NS). FDG-PET is a sensitive and specific test for patients with normal CRP, however, FDG-PET may be false positive if CRP is elevated. Proper patient selection is therefore important. CRP or other parameters indicative of active inflammation appear useful adjuncts for the interpretation of increased FDG-accumulation.

New Molecular Markers for Prostate Tumor Imaging: A Study on 2-Methylene Substituted Fatty Acids as New AMACR Inhibitors†

The development of prostate carcinoma is associated with alterations in fatty acid metabolism. α-Methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme that catalyses interconversion between the (S)/(R)-isomers of a range of α-methylacyl-CoA thioesters. AMACR is involved in the β-oxidation of the dietary branched-chain fatty acids and bile acid intermediates. It is highly expressed in prostate (more than 95 %), colon (92 %), and breast cancers (44 %) but not in the respective normal or hyperplastic tissues. Thus, targeting of AMACR could be a new strategy for molecular imaging and therapy of prostate and some other cancers. Unlabeled 2-methylenacyl-CoA thioesters (12 a-c) were designed as AMACR binding ligands. The thioesters were tested for their ability to inhibit the AMACR-mediated epimerization of (25R)-THC-CoA and were found to be strong AMACR inhibitors. Radioiodinated (E)-(131) I-13-iodo-2-methylentridec-12-enoic acid ((131) I-7 c) demonstrated preferential retention in AMACR-positive prostate tumor cells (LNCaP, LNCaP C4-2wt and DU145) compared with both AMACR-knockout LNCaP C4-2 AMACR-siRNA and benign BPH1 prostate cell lines. A significant protein-bound radioactive fraction with main bands at 47 (sum of molecular weights of AMACR plus 12 c), 70, and 75 kDa was detected in LNCaP C4-2 wt cells. In contrast, only negligible amounts of protein-bound radioactivity were found in LNCaP C4-2 AMACR-siRNA cells.

ROC analysis for assessment of lesion detection performance in 3D PET: influence of reconstruction algorithms.

Image quality in positron emission tomography (PET) can be assessed with physical parameters, as spatial resolution and signal-to-noise ratio, or using psychophysical approaches, which include the observer performance and the considered task (ROC analysis). For PET in oncology, such a task is the detection of hot lesions. The aim of the present study was to assess the lesion detection performance due to adequate modeling of the scanner and the measurement process in the image reconstruction process. We compared the standard OSEM software of the manufacturer with a sophisticated fully 3D iterative reconstruction technique (USC MAP). A rectangular phantom with 6 oblique line sources in a homogeneous background (2.6 kBq/ml 18F) was imaged dynamically with an ECAT EXACT HR+ scanner in 3D mode. Reconstructed activity contrasts varied between 15 and 0, as the line sources were filled with 11C (3.2 MBq/ml). Measured attenuation and standard randoms, dead time, and scatter corrections of the manufacturer were employed. For the ROC analysis, a software tool presented a cut-out of the phantom (15 x 15 pixels) to two observers. These cut-outs were rated (5 classes) and the area Az under the ROC curve was determined as a measure of detection performance. The improvement for Az with USC MAP compared to the OSEM reconstructions ranged between 0.02 and 0.23 for signal-to-noise ratios of the background between 2.8 and 3.1 and lesion contrast between 2.1 and 4.2. This study demonstrates that adequate modeling of the measurement process in the reconstruction algorithm improves the detection of small hot lesions markedly.